Brentuximab Vedotin in Frontline Therapy of Hodgkin Lymphoma in Patients with Significant Comorbidities Ineligible for Standard Chemotherapy (SGN35-015 Part E)

Brentuximab vedotin (BV) is approved for the treatment of adults with treatment-naïve Stage III or IV classical Hodgkin lymphoma (cHL) combined with doxorubicin, vinblastine, and dacarbazine (AVD) and targets CD30, a receptor expressed on the Reed-Sternberg cells. Treatment with BV plus AVD has demonstrated improved overall survival (OS) with a difference of 4.5 percentage points (6-year OS estimate of 93.9% vs 89.4%) compared with the standard chemotherapy combination of doxorubicin, bleomycin, vinblastine, and dacarbazine (Ansell 2022). For patients (pts) newly diagnosed with cHL, current treatment options have improved pt outcomes in recent years, but survival rates are still very low for those with significant comorbidities. Pts with comorbid conditions can have poor outcomes due to decreased ability to tolerate high dose intensity, increased treatment toxicity, and cHL relapse. This study is evaluating the efficacy and safety of single-agent BV as frontline therapy in pts with cHL who are ineligible for conventional combination chemotherapy due to comorbidities.

SGN35-015 Part E (NCT01716806) is a phase 2, open-label study of BV as frontline cHL therapy. Eligible pts (≥18 years) were unfit for initial conventional combination chemotherapy for cHL as documented by a modified CIRS score ≥10 or requiring assistance or dependence on others for instrumental activities of daily living. Pts were treated with BV (1.8 mg/kg) on Day 1 of each 3-week cycle for up to 16 cycles. The primary endpoint, overall response rate (ORR), was assessed by the investigator according to the Modified Lugano Criteria (Cheson 2014). Key secondary endpoints include safety, duration of response (DOR), complete response (CR) rate using the Modified Lugano Criteria (Cheson 2014), progression-free survival (PFS), and OS.

Twenty-eight pts with cHL were treated with BV. Median age was 76 years (range, 54 to 93 years) and pts most frequently had a disease stage of II (36%), an ECOG performance status of ≥2 (47%; 29% and 18% had an ECOG performance status of 2 and 3, respectively), and were female (57%). The ORR was 20 (71%) of 28 treated pts (95% CI: 51.3%, 86.8%), including 5 pts with a CR (18%) and 15 pts with a partial response (54%). Two pts did not respond to treatment: 1 with progressive disease (4%) and 1 with stable disease (4%); the remaining six pts did not have post-baseline responses (21%), either due to deaths before first scheduled response assessment or not yet reaching first scheduled response assessment. Median DOR was 6.5 months (95% CI: 3.7 months, not estimable) and median PFS was 7.4 months (95% CI: 3.1 months, 11.6 months). At a median follow-up of 8.5 months (range, 0.1 to 31.3 months), the 2-year OS rate was 73% (95% CI: 47%, 88%).

At a median treatment duration of 18 weeks (range, 0 to 49 weeks), 16 pts (57%) experienced treatment-emergent adverse events (TEAEs) ≥ Grade 3. The most common ≥ Grade 3 TEAEs were fatigue (n=3; 11%), acute kidney injury, anemia, atrial fibrillation, back pain, hypoxia, pneumonia, sepsis, syncope, and vomiting (n=2 each; 7%). Six pts (21%) discontinued treatment due to a TEAE; 1 death due to a TEAE (failure to thrive) was considered treatment-related.

In patients with cHL who are unfit for initial conventional chemotherapy and have poor survival outcomes due to comorbidities, BV monotherapy as frontline treatment appears effective and has an acceptable safety profile. Additionally, there appears to be no significant difference in OS by ECOG status based on current analysis. The study is currently enrolling.

Yasenchak:Seagen Inc.: Consultancy, Research Funding; Beigene: Speakers Bureau; Takeda: Research Funding. Bordoni:Chairman Annual Precision Oncology Symposium: Other; Northside Hospital Cancer Institute: Other: Travel Expenses; Janssen Biotech: Speakers Bureau; OneLive Clinical Congress Consultants: Speakers Bureau; NeoGenomics Labs: Speakers Bureau; Phillips Gilmore Oncology: Consultancy; Oncocyte: Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses; Sanofi US: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Speakers Bureau; Guardant Health: Consultancy, Speakers Bureau. Patel-Donnelly:Boston Biomed: Research Funding; Gilead: Research Funding; LAM Therapeutics: Research Funding; Roche: Research Funding; American Board of Internal Medicine (ABIM): Other: American Board of Internal Medicine (ABIM). Goldschmidt:Amgen: Consultancy; G1 Therapeutics: Consultancy, Speakers Bureau; TG Therapeutics: Consultancy; Ontada: Current Employment; Blue Ridge Cancer Care: Current Employment; AstraZeneca: Consultancy; Bristol-Meyers Squibb: Speakers Bureau. Boccia:AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Speakers Bureau; Rigel: Consultancy, Honoraria, Research Funding, Speakers Bureau; Regeneron: Speakers Bureau; Sanofi: Speakers Bureau; Genmab: Consultancy, Honoraria, Speakers Bureau; Bristol Myers Squibb: Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Karyopharm: Speakers Bureau; Incyte: Consultancy, Honoraria, Research Funding, Speakers Bureau; Genentech: Consultancy, Honoraria, Research Funding, Speakers Bureau; Daiichi Sankyo: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Cline:Texas Oncology: Current Employment; Reflexion Medical: Consultancy, Other: Travel Expenses; Pfizer: Honoraria. Mamidipalli:Seagen Inc.: Current Employment. Liu:Seagen: Current Employment, Current equity holder in publicly-traded company. Beck:Highlands Oncology Group: Research Funding.